Interpretive Summary: The time-course pattern and gender effect of immune and stress hormone responses to an infectious challenge were analyzed using a pig model. Secretion of the pro-inflammatory immune-associated agents increased in a time-dependent manner following infection. There was also a time-dependent increase in secretion of the stress-related hormones cortisol, epinephrine (E), and norepinephrine (NE) following infection, with peak concentrations attained within 30 min. The magnitude of the immune-associated agents TNF-alpha and IL-beta were both positively associated with the magnitude of cortisol response following infection, whereas IL-1beta and IL-6 were positively correlated with the magnitude of E and NE responses following infection. Acute phase protein production was also time-dependently increased following infection. The concentration of immune cells in circulation was decreased at 5.5 h post-infection and negatively correlated with pro-inflammatory cytokine production. By 24 h post-infection, immune cell counts increased and were positively associated with both pro-inflammatory cytokine and stress hormone production. The amplitude of pro-inflammatory cytokine response following infection was affected by gender; however, the magnitude of elevated immune-associated agents was not. The magnitude of the NE response, but not of the E and cortisol responses, to infection was influenced by gender (P < 0.05). Similar to the pro-inflammatory response, the magnitude of exposure to the stress hormones following infection was not influenced by gender. Collectively, these results demonstrate gender-specific changes over time in innate immune- and stress-related hormones.

Technical Abstract:
The temporal pattern and gender effect of immune and stress hormone responses to a lipopolysaccharide (LPS) challenge were assessed using a pig model. Secretion of the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 increased in a time-dependent manner following LPS infusion. There was also a time-dependent increase in secretion of the stress-related hormones cortisol, epinephrine (E), and norepinephrine (NE) following LPS with peak concentrations attained within 30 min. The magnitude of the TNF-alpha and IL-beta responses were both positively associated (P < 0.05) with the magnitude of cortisol response following LPS, whereas serum IL-1beta and IL-6 were positively correlated with the magnitude of E and NE responses following LPS. Acute phase protein production was also time-dependently increased following LPS. The concentration of immune cells in circulation was decreased (P < 0.05) at 5.5 h post-LPS and negatively correlated with pro-inflammatory cytokine production. By 24 h post-LPS, immune cell counts increased (P < 0.05) and were positively associated with both pro-inflammatory cytokine and stress hormone production. The amplitude of pro-inflammatory cytokine response following LPS was affected (P < 0.05) by gender classification; however, the magnitude of elevated cytokine concentrations was not. The magnitude of the NE response, but not of the E and cortisol responses, to LPS was influenced by gender (P < 0.05). Similar to the pro-inflammatory cytokines, the magnitude of exposure to the stress hormones following LPS was not influenced by gender. The production of serum amyloid A (SAA) was influenced by gender with barrows producing more SAA at 24 h post-LPS than gilts (P < 0.05). Collectively, these results demonstrate gender-specific concomitant temporal changes in innate immune- and stress-related hormones.